Recent transmission clustering of HIV-1 C and CRF17_BF strains characterized by NNRTI-related mutations among newly diagnosed men in central Italy

Increased evidence of relevant HIV-1 epidemic transmission in European countries is being reported, with an increased circulation of non-B-subtypes. Here, we present two recent HIV-1 non-B transmission clusters characterized by NNRTI-related amino-acidic mutations among newly diagnosed HIV-1 infected men, living in Rome (Central-Italy)

Preventing future pandemics and epidemics through a North-South collaboration on genomic surveillance in Africa

The editorial describes the measures for preventing future pandemics and epidemics through a North-South collaboration on genomic surveillance in Afric

Impact of analytical treatment interruption on burden and diversification of HIV peripheral reservoir: a pilot study

Background: If analytical antiretroviral-treatment (ART) interruption (ATI) might significantly impact quantitative or qualitative peripheral-total HIV-DNA is still debated. Methods: Six chronically HIV-1 infected patients enrolled in APACHE-study were analysed for peripheral-total HIV-DNA and residual viremia, major-resistance-mutations (MRMs) and C2-V3-C3 evolution at pre-ATI (T1), during ATI (T2) and at achievement of virological success after ART-resumption (post-ATI, T3). These data were obtained at three comparable time-points in five chronically HIV-1 infected patients on suppressive ART for ≥1 year, enrolled in MODAt-study. Results: At T1, APACHE and MODAt individuals had similar peripheral-total HIV-DNA and residual viremia (p = 0.792 and 0.662, respectively), and no significant changes for these parameters were observed between T1 and T3 in both groups. At T1, 4/6 APACHE and 2/5 MODAt carried HIV-DNA MRMs. MRMs disappeared at T3 in 3/4 APACHE. All disappearing MRMs were characterized by T1 intra-patient prevalence <80%, and mainly occurred in APOBEC3-related sites. All MRMs persisted over-time in the 2 MODAt. C2-V3-C3 genetic-distance significantly changed from T1 to T3 in APACHE individuals (+0.36[0.11-0.41], p = 0.04), while no significant changes were found in MODAt. Accordingly, maximum likelihood trees (bootstrap > 70%) and genealogical sorting indices (GSI > 0.50 with p-value < 0.05) showed that T1 C2-V3-C3 DNA sequences were distinct from T2 and T3 viruses in 4/6 APACHE. Virus populations at all three time-points were highly interspersed in MODAt. Conclusions: This pilot study indicates that short ATI does not alter peripheral-total HIV-DNA burden and residual viremia, but in some cases could cause a genetic diversification of peripheral viral reservoir in term of both MRMs rearrangement and viral evolution

Evaluation of HIV-1 integrase resistance emergence and evolution in patients treated with integrase inhibitors.

Abstract Objectives We evaluated the emergence of mutations associated to integrase strand transfer inhibitors (INSTI) resistance (INSTI-RMs) and the integrase evolution in HIV-1 infected patients treated with this drug class. Methods Emergence of INSTI-RMs and integrase evolution (estimated as genetic distance between integrase sequences under-INSTI and before-INSTI treatment) were evaluated in 107 INSTI-naive patients (19 drug-naive and 88 drug-experienced) with two plasma genotypic resistance tests available: one before and one under INSTI treatment. A logistic regression analysis was performed to evaluate factors associated with the integrase evolution under INSTI treatment. Results Patients were mainly infected by B subtype (72.0%). 87 patients were treated with raltegravir, 13 with dolutegravir and 7 with elvitegravir. Before INSTI treatment, one patient harboured the major INSTI-RM R263 K, and three patients the accessory INSTI-RMs T97A. Under INSTI treatment, the emergence of ≥1 INSTI-RM was found in 39 (36.4%) patients. The major INSTI-RMs which emerged more frequently were: N155H (17.8%), G140S (8.4%), Y143R (7.5%), Q148H (6.5%), Y143C (4.7%). Concerning integrase evolution, a higher genetic distance was found in patients with ≥1 INSTI-RM compared to those without emergence of resistance (0.024 [0.012-0.036] vs. 0.015 [0.009-0.024], p = 0.018). This higher integrase evolution was significantly associated with a longer duration of HIV-1 infection, a higher number of past regimens and non-B subtypes. Conclusions Our findings confirmed that in INSTI-naive patients, major INSTI-RMs occur very rarely. Under INSTI treatment, selection of drug-resistance follows the typical drug-resistance pathways; a higher evolution characterizes integrase sequences developing drug-resistance compared to those without any resistance

External quality assessment of HIV-1 DNA quantification assays used in the clinical setting in Italy

none18no: Total cell-associated HIV-1 DNA is a surrogate marker of the HIV-1 reservoir, however, certified systems for its quantification are not available. The Italian HIV DNA Network was launched to validate HIV-1 DNA quantification methods in use at University and Hospital labs. A quality control panel including HIV-1 DNA standards, reconstructed blood samples (RBSs) and DNA from different HIV-1 subtypes was blindly tested by 12 participating labs by quantitative real-time PCR (n = 6), droplet digital PCR (n = 3) or both (n = 3). The median 95% hit rate was 4.6 (3.7-5.5) copies per test and linearity in the tested range was excellent (R2 = 1.000 [1.000-1.000]). The median values obtained across labs were 3,370 (2,287-4,245), 445 (299-498), 59 (40-81) and 7 (6-11) HIV-1 DNA copies, for the 3,584, 448, 56 and 7-copy standards, respectively. With RBSs, measured values were within twofold with respect to the median in two thirds of cases. HIV-1 subtypes were missed (CRF01_AE by 3 labs) or underestimated by > 1 log (subtypes A, C, D, F by one lab; CRF01_AE by one lab; CRF02_AG by one lab). The overall performance was excellent with HIV-1 DNA standards, however detection of different HIV-1 subtypes must be improved.openVicenti, Ilaria; Dragoni, Filippo; Giannini, Alessia; Casabianca, Anna; Lombardi, Francesca; Di Sante, Laura; Turriziani, Ombretta; Racca, Sara; Paolucci, Stefania; Lai, Alessia; Bon, Isabella; Abbate, Isabella; Rozera, Gabriella; Belmonti, Simone; Scutari, Rossana; Alteri, Claudia; Saladini, Francesco; Zazzi, MaurizioVicenti, Ilaria; Dragoni, Filippo; Giannini, Alessia; Casabianca, Anna; Lombardi, Francesca; Di Sante, Laura; Turriziani, Ombretta; Racca, Sara; Paolucci, Stefania; Lai, Alessia; Bon, Isabella; Abbate, Isabella; Rozera, Gabriella; Belmonti, Simone; Scutari, Rossana; Alteri, Claudia; Saladini, Francesco; Zazzi, Maurizi

Docking Analysis and Resistance Evaluation of Clinically Relevant Mutations Associated with the HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors Nevirapine, Efavirenz and Etravirine

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A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naïve patients

Little is known about SARS-CoV-2 evolution under Molnupiravir and Paxlovid, the only antivirals approved for COVID-19 treatment. By investigating SARS-CoV-2 variability in 8 Molnupiravir-treated, 7 Paxlovid-treated and 5 drug-naive individuals at 4 time-points (Days 0-2-5-7), a higher genetic distance is found under Molnupiravir pressure compared to Paxlovid and no-drug pressure (nucleotide-substitutions/site mean & PLUSMN;Standard error: 18.7 x 10(-4) & PLUSMN; 2.1 x 10(-4) vs. 3.3 x 10(-4) & PLUSMN; 0.8 x 10(-4) vs. 3.1 x 10(-4) & PLUSMN; 0.8 x 10(-4), P = 0.0003), peaking between Day 2 and 5. Molnupiravir drives the emergence of more G-A and C-T transitions than other mutations (P = 0.031). SARS-CoV-2 selective evolution under Molnupiravir pressure does not differ from that under Paxlovid or no-drug pressure, except for orf8 (dN > dS, P = 0.001); few amino acid mutations are enriched at specific sites. No RNA-dependent RNA polymerase (RdRp) or main proteases (Mpro) mutations conferring resistance to Molnupiravir or Paxlovid are found. This proof-of-concept study defines the SARS-CoV-2 within-host evolution during antiviral treatment, confirming higher in vivo variability induced by Molnupiravir compared to Paxlovid and drug-naive, albeit not resulting in apparent mutation selection

Genetic divergence of HIV-1 B subtype in Italy over the years 2003\u20132016 and impact on CTL escape prevalence

HIV-1 is characterized by high genetic variability, with implications for spread, and immune-escape selection. Here, the genetic modification of HIV-1 B subtype over time was evaluated on 3,328 pol and 1,152 V3 sequences belonging to B subtype and collected from individuals diagnosed in Italy between 2003 and 2016. Sequences were analyzed for genetic-distance from consensus-B (Tajima-Nei), non-synonymous and synonymous rates (dN and dS), CTL escapes, and intra-host evolution over four time-spans (2003\u20132006, 2007\u20132009, 2010\u20132012, 2013\u20132016). Genetic-distance increased over time for both pol and V3 sequences (P < 0.0001 and 0.0003). Similar results were obtained for dN and dS. Entropy-value significantly increased at 16 pol and two V3 amino acid positions. Seven of them were CTL escape positions (protease: 71; reverse-transcriptase: 35, 162, 177, 202, 207, 211). Sequences with 653 CTL escapes increased from 36.1% in 2003\u20132006 to 54.0% in 2013\u20132016 (P < 0.0001), and showed better intra-host adaptation than those containing 642 CTL escapes (intra-host evolution: 3.0 7 10 123 [2.9 7 10 123\u20133.1 7 10 123] vs. 4.3 7 10 123 [4.0 7 10 123\u20135.0 7 10 123], P[LRT] < 0.0001[21.09]). These data provide evidence of still ongoing modifications, involving CTL escape mutations, in circulating HIV-1 B subtype in Italy. These modifications might affect the process of HIV-1 adaptation to the host, as suggested by the slow intra-host evolution characterizing viruses with a high number of CTL escapes

Pre-Treatment HIV Drug Resistance and Genetic Diversity in Cameroon: Implications for First-Line Regimens

the efficacy of first-line antiretroviral therapy (ART) may be hampered by the presence of HIV drug resistance (HIVDR). we described HIV-1 pre-treatment drug resistance (PDR) patterns, effect of viral clades on PDR, and programmatic implications on first-line regimens in cameroon. a sentinel surveillance of PDR was conducted from 2014 to 2019. sequencing of HIV-1 protease and reverse transcriptase was performed, and HIVDR was interpreted using stanford HIVdb.v.9.4. In total, 379 sequences were obtained from participants (62% female, mean age 36 +/- 10 years). the overall PDR rate was 15.0% [95% CI: 11.8-19.0] nationwide, with significant disparity between regions (p = 0.03). NNRTI PDR was highest (12.4%), of which 7.9% had DRMs to EFV/NVP. two regions had EFV/NVP PDR above the 10% critical threshold, namely the far north (15%) and east (10.9%). Eighteen viral strains were identified, predominated by CRF02_AG (65.4%), with no influence of genetic diversity PDR occurrence. TDF-3TC-DTG predictive efficacy was superior (98.4%) to TDF-3TC-EFV (92%), p &lt; 0.0001. the overall high rate of PDR in cameroon, not substantially affected by the wide HIV-1 genetic diversity, underscores the poor efficacy of EFV/NVP-based first-line ART nationwide, with major implications in two regions of the country. this supports the need for a rapid transition to NNRTI-sparing regimens, with TDF-3TC-DTG having optimal efficacy at the programmatic level

Induction of immune response after SARS-CoV-2 mRNA BNT162b2 vaccination in healthcare workers

[no abstract available